ATP13A2

SV Health Investors, fresh off a $250 million fund for dementia-focused biotechs, has unveiled its latest effort, this time to advance new Parkinson’s disease treatments. The London-based healthcare investor launched Endlyz Therapeutics on Monday morning. The small biotech, which has quietly been in the works for nearly four years, is working on Parkinson’s disease and other neurodegenerative disorders by revamping the body’s cellular recycling function. The startup has raised $16 million to date from SV’s Dementia Discovery Fund, Oxford Science Enterprises, AbbVie Ventures, Parkinson’s UK and the Centre for Drug Design and Discovery at KU Leuven, according to a source familiar with the biotech’s fundraising. SV’s DDF has backed more than 20 biotechs, including Caraway Therapeutics (now owned by Merck), the late-stage Parkinson’s biotech Cerevance, and QurAlis, which has partnered with Eli Lilly. Through its investment from AbbVie’s corporate VC arm, Endlyz has now established ties with a big pharma that’s been increasingly active in neuroscience in recent years. AbbVie’s acquisitions of late include Cerevel , Aliada Therapeutics and Mitokinin . Endlyz is working on small molecule modulators of ATP13A2 and ATP10B. The polyamine and lipid transporter enzymes, respectively, are key to maintaining neuronal health. “Both targets are linked to human genetic validation, and we know that they give the right phenotypes and disease conditions that are also recapitulated in Parkinson’s disease,” Endlyz CEO and co-founder Joanna Wolak said in an interview. Caraway had a preclinical program in the ATP13A2 space when Merck bought the startup for up to $610 million in 2023. A Merck spokesperson declined to comment about the status of the program. The startup is beginning to fundraise a Series A, with a goal of getting its first candidate in the clinic in 2027, Wolak said. It’s also open to pharma collaborations and an “early exit” to an acquirer, she added. Endlyz said it’s also working with the Michael J. Fox Foundation, which gave the company a research grant to help identify biomarkers as it gets toward clinical development. Endlyz’s scientific co-founders include Wolak, KU Leuven professor Peter Vangheluwe, and University of Oxford professors Richard Wade-Martins and John Davis.

Collaboration with KU Leuven, [led by global leader Peter Vangheluwe, PhD, a longstanding partner of The Michael J. Fox Foundation] will leverage Large Quantitative Models (LQMs) and other advanced AI technologies to design and rapidly screen potential new drug compounds PALO ALTO, Calif., Oct. 29, 2024 /PRNewswire/ -- SandboxAQ announced today that The Michael J. Fox Foundation for Parkinson's Research (MJFF) has selected the company's AI platform to accelerate the identification of compounds that activate a gene linked to Parkinson's disease (PD). SandboxAQ's team of computational chemists and machine learning experts will collaborate with the Vangheluwe lab and CD3 at Belgium-based KU Leuven to identify activators for ATP10B. Peter Vangheluwe is a global leader in lysosomal transporters that are implicated in Parkinson's disease, such as ATP13A2 and ATP10B. As a long-standing MJFF partner, the Vangheluwe lab has helped to better understand the underlying mechanisms of ATP13A2 and ATP10B dysfunction in Parkinson's disease and pioneered drug discovery efforts on ATP13A2. ATP10B is a novel candidate risk gene for PD encoding a sphingolipid-transporting ATPase involved in neuronal lipid homeostasis. As a member of the P4-ATPase family, it flips glucosylceramide across the lysosomal membrane, maintaining essential cellular functions. Despite its potential as a therapeutic target, drug discovery efforts face challenges due to ATP10B's multiunit structural complexity, poor expression and difficult handling and limited understanding of its large-scale reorganization during a complex functional cycle. Targeting ATP10B requires novel approaches to identify small molecule modulators capable of restoring its function. "Leveraging innovative technology in Parkinson's research and fostering a collaboration with leading experts] is one of the many ways MJFF works to enable a diverse pipeline of treatments for people with Parkinson's disease," said Michelle Durborow, head of research operations, MJFF. "We look forward to this collaboration with SandboxAQ and KU Leuven to unlock novel treatments for PD." SandboxAQ's Large Quantitative Models (LQMs) integrate active learning with physics-based scoring functions to create detailed protein profiles and complex interaction matrices. This approach enables rapid in silico high-throughput screening of millions of available compounds to identify potential modulators of ATP10B's function. Leveraging their expertise in challenging protein targets, SandboxAQ will also support assay development and optimization, generate actionable hypotheses for ATP10B activation and advance early-stage drug discovery efforts on a remarkably complex target with major implications in neurodegenerative diseases. "SandboxAQ's Large Quantitative Models and AI simulation techniques have proven their ability to rapidly identify ligands and design novel molecules for other challenging neurodegenerative diseases such as Alzheimer's," said Nadia Harhen, GM of AI Simulation at SandboxAQ. "KU Leuven hosts one of the world's foremost research labs for Parkinson's disease, and we're eager to apply our Large Quantitative Models to their existing efforts, accelerating new breakthrough treatments for PD." KU Leuven researchers, in collaboration with the Centre for Drug Design and Discovery (CD3) of KU Leuven, have taken the first steps to unlock the ATP10B protein for small molecule drug discovery since first describing the gene in 2020. Despite significant advances in understanding the biology of ATP10B, the protein has proven difficult to study. Also, there is little real-world data available related to this specific class of lipid flippases that researchers can use to identify the most effective compounds. SandboxAQ's Quantitative AI simulations can generate accurate data that enable a more efficient search of the vast chemical space to find and develop compounds with the correct profile. "The ability to simulate a drug compound's effects on ATB10B and analyze its mode of action will greatly accelerate our groundbreaking research, helping us achieve with AI technology what lab experimentation alone could not," said Peter Vangheluwe, professor and head of the Laboratory of Cellular Transport Systems at KU Leuven. "SandboxAQ's technology has opened the door to a new way of designing novel molecules from the vast chemistry space and testing our hypotheses with unprecedented speed and accuracy, delivering previously unknowable insights that will guide our research." About SandboxAQ SandboxAQ is a B2B company delivering AI solutions that address some of the world's greatest challenges. The company's Large Quantitative Models (LQMs) deliver critical advances in life sciences, financial services, navigation, cyber and other sectors. The company emerged from Alphabet Inc. as an independent, growth capital-backed company in 2022, funded by leading investors including T. Rowe Price, Eric Schmidt, Breyer Capital, Guggenheim Partners, Marc Benioff, Thomas Tull, Section32, and others. For more information, visit . About KU Leuven KU Leuven boasts a rich tradition of education and research spanning six centuries. Recognized with the European HR Excellence in Research Award, the university's commitment to fundamental research remains unwavering. Simultaneously, KU Leuven stays attuned to contemporary cultural, economic, and industrial developments, as well as the needs and expectations of the community. As Belgium's largest university in terms of research funding and expenditure, KU Leuven is a proud charter member of LERU. The university excels in both fundamental and applied research across all academic disciplines, maintaining a strong international orientation. In the Times Higher Education 2023 ranking, KU Leuven was ranked as the 14th best European university. Additionally, for four consecutive years, it has been recognized as the most innovative university in Europe by Reuters' Top 100 of the World's Most Innovative Institutions. The Lab of Cellular Transport Systems (LCTS), led by Prof. Dr. Peter Vangheluwe, is dedicated to advancing our understanding of cellular transport mechanisms. The lab focuses on the unique molecular properties of P-type ATPases and their crucial roles in health and disease. Through cutting-edge research, LCTS aims to uncover the physiological functions of these transport systems, contributing to the development of novel therapeutic strategies for various diseases. The Centre for Drug Design and Discovery (CD3) is a pioneering drug discovery centre and investment fund. KU Leuven Research & Development and the European Investment Fund created CD3 in 2006 to drive the translation of innovative basic research to the clinic. With a focus on the discovery and development of new medicines, CD3 supports academic research groups and small companies by providing expert drug discovery capabilities and financial resources. The center has successfully launched multiple investment funds, including a €70 million fund (CD3 IV) in 2023 to expand its scope and impact. SOURCE SandboxAQ WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Merck & Co. agreed to acquire Caraway Therapeutics for up to $610 million, bolstering its pipeline with a number of preclinical small-molecule compounds mainly focused on Parkinson’s disease. The deal announced Tuesday includes an undisclosed upfront payment as well as milestones linked to certain experimental drugs.“Caraway’s multidisciplinary approach has yielded important progress in evaluating novel mechanisms of modulation of lysosomal function with potential for the treatment of progressive neurodegenerative diseases,” remarked George Addona, senior vice president for discovery, preclinical development and translational medicine at Merck Research Laboratories.Caraway’s pipeline includes two compounds targeting the TRPML1 ion channel, with one focused on GBA-Parkinson’s disease and the other on an undisclosed non-CNS rare disease. The other two preclinical assets targeting TMEM175 and ATP13A2 are under development for Parkinson’s disease, with the former also being investigated for amyotrophic lateral sclerosis.In 2021, AbbVie paid $17 million upfront for an option on Caraway’s programme targeting the lysosomal potassium ion channel TMEM175. Meanwhile, Merck has been a shareholder of Caraway since 2018 through its MRL Ventures Fund.